crossing96/oncoscreening huggingface dataset:
The preclinical activity of lenalidomide in indolent urothelial carcinoma.	BACKGROUND: Lenalidomide is an IMiD® immunomodulatory drug, which may warrant evaluation in urothelial carcinoma (UC). MATERIALS AND METHODS: The in vitro and in vivo activity of lenalidomide was evaluated in human and murine UC cell lines. Tumors were evaluated by immunohistochemistry for (CD31), cleaved caspase-3 (CC3) and CD3+/CD20+ lymphocyte infiltration. Cereblon, a molecular target of lenalidomide was analyzed by immunohistochemistry. RESULTS: Significant pro-apoptotic activity, and reduction of cell viability was seen at low micromolar concentrations of lenalidomide against indolent human RT4 UC cells in vitro. Cereblon expression was quantitatively lower in sensitive RT4 cells compared to resistant 5637 cells. In RT4 xenografts, lenalidomide significantly reduced tumor size and CD31 expression, and increased expression of CC3 (p<0.05). Cereblon expression increased in lenalidomide-treated RT4 xenografts (p<0.05). CONCLUSION: Lenalidomide demonstrated preclinical activity against superficially-invasive low-grade UC cells attributable to direct tumor cell apoptosis and anti-angiogenic activity. Clinical trials are warranted in patients with indolent UC.	bladder
Sex steroids and gender differences in nonmuscle invasive bladder cancer.	PURPOSE OF REVIEW: To review and summarize current knowledge on gender differences and sex steroid hormones in nonmuscle invasive bladder cancer. RECENT FINDINGS: Beyond the proven role of gender as a risk factor for the development of bladder cancer, recent studies indicate that women present with more advanced bladder cancer tumor stages than men, which may be due to differences in both bladder cancer care and biology. In addition, female gender has been identified as an independent prognostic factor for both recurrence and progression and may be associated with worse response to Bacillus Calmette-Guérin instillation therapy. Overall, sex steroid hormones and their receptors impact bladder carcinogenesis, recurrence and progression. Basic and transitional research evidence suggests that estrogens may initially protect against bladder cancer development, but later promote bladder cancer progression. Androgens, in contrast, seem to initiate and drive bladder cancer with its receptor playing a central role. Promising novel research shows a potential role of sex steroid hormones as therapeutic targets. SUMMARY: Whereas men are more likely to develop bladder cancer, women present generally with more advanced disease and have worse oncologic outcomes even after adjusting for tumor stage. Sex steroid hormones and their receptors play an active role in bladder cancer development and progression and represent attractive therapeutic targets for gender-specific care.	bladder
Underutilization of immediate intravesical chemotherapy following TURBT: results from NSQIP.	INTRODUCTION: A single perioperative dose of intravesical chemotherapy (IVC) following transurethral resection of bladder tumors (TURBT) for non-muscle invasive bladder cancer has demonstrated a reduction in tumor recurrence. In this study, we investigate the contemporary (2010) utilization of IVC following TURBT using a prospective national database. MATERIALS AND METHODS: Using the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, we identified patients with bladder cancer using ICD-9 codes. From this group, patients undergoing TURBT based on Current Procedural Terminology (CPT) codes were analyzed. We then identified those patients who underwent TURBT and also received intravesical therapy. Operative time, length of hospital stay, and perioperative complications were evaluated. RESULTS: From January 1 to December 31, 2010, 1273 patients at participating ACS-NSQIP sites underwent TURBT for bladder cancer. There were 417 (33%) small, 486 (38%) medium, and 370 (29%) large tumors treated. In total, 33 (2.6%) patients received IVC. When comparing patients who received perioperative IVC to those who did not, there was no difference in median operative times (27 mins versus 28 mins, p = 0.899). There was one urinary tract infection in the IVC group. CONCLUSIONS: IVC remains greatly underutilized despite current data documenting its efficacy in reducing tumor recurrence for TaT1 bladder cancer. Instillation of IVC following TURBT does not increase morbidity. Our findings support the continued need to explore ways of improving rates of perioperative IVC administration following TURBT.	bladder
CT urography and hematuria: a retrospective analysis of 771 patients undergoing CT urography over a 1-year period.	BACKGROUND: Computed tomography (CT) urography is now used in the work-up of patients with hematuria. The dose of contrast medium and radiation varies considerably between the different CT protocols. PURPOSE: To study the disease prevalence in a consecutive group of patients with hematuria undergoing CT urography with a low dose of contrast medium and radiation. MATERIAL AND METHODS: From 1 April 2007 to 31 March 2008, using the Radiological Information System (RIS) as well as electronic patient records, demographic data, reason for referral, and diagnosis were obtained for all patients undergoing CT urography due to hematuria. The patients were followed for 3 years. RESULTS: A total of 771 patients had hematuria diagnosed at the time of referral. In 137 patients (18%), a tumor and / or a complex cyst was found in the urinary tract (renal, ureteral, or bladder), in 68 (9%) a calculi, in 118 (15%) other disease (i.e. infection or anomaly) was found. No abnormalities were found at CT urography in 455 (58%) of the patients with hematuria. Lesions were found more frequently in patients with visible hematuria than in patients with non-visible hematuria (48% vs. 29%). No malignant tumor or complex cyst was found in the kidneys or the ureters in patients with nonvisible hematuria. CONCLUSION: CT urography with its low dose of contrast medium and radiation is a useful diagnostic imaging test for investigating patients with hematuria.	bladder
Duration and intensity of tobacco smoking and the risk of papillary and non-papillary transitional cell carcinoma of the bladder.	PURPOSE: To evaluate the impact of tobacco smoking on specific histological subtypes of transitional cell carcinoma of the bladder (TCC). METHODS: Between 2003 and 2009, we conducted a hospital-based case-control study in Italy, enrolling 531 incident TCC cases and 524 cancer-free matched patients. Odds ratios (OR) and corresponding 95% confidence intervals (CI) were estimated through multiple logistic regression models. RESULTS: Compared to never smokers, TCC risk was threefold higher in former smokers (95% CI 2.07-4.18) and more than sixfold higher in current smokers (95% CI 4.54-9.85). TCC risk steadily increased with increasing intensity (OR for ≥25 cigarettes/day 8.75; 95% CI 3.40-22.55) and duration of smoking (OR for ≥50 years 5.46; 95% CI 2.60-11.49). No heterogeneity emerged between papillary and non-papillary TCCs for smoking intensity and duration, but the risk for those who had smoked for ≥50 years was twice for non-papillary TCC (OR 10.88) compared with papillary one (OR 4.76). Among current smokers, the risk for a 10-year increase in duration grew across strata of intensity (p-trend = 0.046). Conversely, the risk for a 5-cigarette/day increase in smoking intensity was quite steady across strata of duration (p-trend = 0.18). CONCLUSIONS: Study results suggested that duration of smoking outweighs intensity in determining TCC risk, with limited differences across histological subtypes. Elimination of tobacco smoking may prevent about 65 % of TCCs.	bladder
Impaired estimated glomerular filtration rate is a significant predictor for non-muscle-invasive bladder cancer recurrence and progression--introducing a novel prognostic model for bladder cancer recurrence.	PURPOSE: To evaluate the influence of preoperative patient-associated parameters and comorbidities, with special focus on preoperative renal function on non-muscle-invasive bladder carcinoma (NMIBC) recurrence and progression. PATIENTS AND METHODS: Medical records of 192 patients with first diagnosis of NMIBC from 1996 to 2006 treated at our department were reviewed for tumor stage and grade, comorbidities, and putative preoperative risk factors (diabetes mellitus, smoking habits, C-reactive protein levels, estimated glomerular filtration rate [eGFR] by chronic kidney disease-epidemiology collaboration formula, patient age, and sex). RESULTS: Median follow-up was 80 months. Tumor recurrence was observed in 104 patients (54%); progression to higher pT category or grade was found in 43 patients (22%). Overall, 20 (10%) patients had progression to category pT2, with a median time to progression of 11 months (95% CI: 3.16-55.77). Overall, median time to recurrence was 11.91 months (8.00-14.94), while median time to progression to higher category/grade was 15 months (8.60-36.95). Cancer-specific death was recorded for 12 patients (6%). Univariate analysis revealed category, grade, and eGFR < 60 ml/min as significant predictive determinants for recurrence, overall progression, and progression to pT2-category disease. Based on the results of multivariate analysis, a risk factor model was created to classify patients with high and low risk of recurrence. CONCLUSIONS: eGFR is a significant predictive variable of NMIBC recurrence and progression. Integrating eGFR into NMIBC risk calculation helped to discriminate individuals with high and low risk of cancer recurrence. Confirmatory studies and external validation are needed to corroborate these findings. Furthermore, the role of tumor multifocality and size should be analyzed for the proposed prediction model.	bladder
Bladder biopsy of normal-appearing mucosa is not helpful in patients with unexplained positive cytology after nonmuscle invasive bladder cancer.	PURPOSE: Malignant voided cytology with normal endoscopic evaluation represents a diagnostic and therapeutic challenge in many patients with a history of nonmuscle invasive bladder cancer. Bladder biopsy is often advised but its efficacy is unclear. We evaluated the usefulness of bladder biopsy in patients with unexplained positive cytology and describe recurrence patterns in this unique patient subset. MATERIALS AND METHODS: From an institutional database we retrospectively identified patients with a history of nonmuscle invasive bladder cancer and surveillance cystoscopy from 2008 to 2012 who had malignant voided urine cytology but normal cystoscopy. Patients underwent systematic bladder biopsy or cystoscopic surveillance and were followed for recurrence and progression. RESULTS: Of 444 patients 343 were followed with surveillance only and 101 underwent a total of 118 biopsies of normal-appearing bladder mucosa. Three biopsies (2.5%) showed carcinoma in situ and none revealed invasive carcinoma. During the median 32-month followup recurrence developed in the bladder in 194 patients (44%), in the upper tract in 24 (5%) and in the prostatic urethra in 5 (1%) while 219 (49%) had no recurrence. A previous diagnosis of upper tract urothelial carcinoma and a history of bacillus Calmette-Guérin treatment were associated with an increased recurrence risk on multivariate analysis. Recurrence rates and patterns were similar in the biopsy and surveillance groups. CONCLUSIONS: Patients with malignant cytology despite normal cystoscopy have a high recurrence rate. Biopsy of normal-appearing bladder mucosa in this setting is rarely positive and does not alter the recurrence pattern.	bladder
Prognostic significance of heme oxygenase-1, S100 calcium-binding protein A4, and syndecan-1 expression in primary non-muscle-invasive bladder cancer.	"We investigated the prognostic significance of heme oxygenase-1 (HO-1), S100 calcium-binding protein A4 (S100A4), and syndecan-1 (SYND1) expression in patients with primary non-muscle-invasive bladder cancer (NMIBC). Immunohistochemical studies were performed on tissue specimens from 109 patients diagnosed with primary NMIBC following complete transurethral resection, with the expression dichotomized as negative/mild (""low"") versus moderate/strong (""high"") according to scores based on staining area and intensity. The effect of each biomarker on recurrence-free survival (RFS) and progression-free survival (PFS) was analyzed. The predictive accuracy for RFS and PFS in multivariate Cox regression models with or without (the baseline model) biomarkers was estimated using the Harrell concordance index. High HO-1, S100A4, and SYND1 expressions were observed in 33.0%, 36.7%, and 63.3% cases, respectively. High HO-1 and S100A4 expressions were significantly associated with various adverse pathological characteristics (high T stage and grade); SYND1 expression was inversely correlated with these characteristics (all, P < .05). In the baseline multivariate model, multifocality, intravesical therapy, and T stage were significant predictors for RFS, whereas intravesical therapy and T stage had marginal statistical significance in predicting PFS. In the multivariate model with the biomarkers, the 3 biomarkers were significant predictors for RFS; and HO-1 expression was a significant predictor for PFS. Addition of the 3 biomarkers to the baseline model significantly increased the predictive accuracy for RFS from 0.754 to 0.828 (P = .043). Our findings suggest that HO-1, S100A4, and SYND1 expressions have prognostic value in primary NMIBC; thus, their evaluation might be useful for determining treatment strategies."	bladder
Curative therapy for bladder cancer in routine clinical practice: a population-based outcomes study.	AIMS: Definitive therapy of bladder cancer involves cystectomy or radiotherapy; controversy exists regarding optimal management. Here we describe the management and outcomes of patients treated in routine practice. MATERIALS AND METHODS: Treatment records were linked to the Ontario Cancer Registry to identify all cases of bladder cancer in Ontario treated with cystectomy or radiotherapy in 1994-2008. Practice patterns are described in three study periods: 1994-1998, 1999-2003, 2004-2008. Logistic regression, Cox model and propensity score analyses were used to evaluate factors associated with treatment choice and survival. RESULTS: In total, 3879 cases (74%) underwent cystectomy and 1380 (26%) were treated with primary radiotherapy. Cystectomy use increased over time (66, 75, 78%), whereas radiotherapy decreased (34, 25, 22%), P < 0.001. There was substantial regional variation in the proportion of cases undergoing radiotherapy (range 16-51%). Five year cancer-specific survival (CSS) and overall survival were 40 and 36% for surgical cases and 35 and 26% for radiotherapy cases (P < 0.001). In multivariate Cox model and propensity score analyses, there was no significant difference in CSS between surgery and radiotherapy (hazard ratio 0.99, 95% confidence interval 0.91-1.08); radiotherapy was associated with slightly inferior overall survival (hazard ratio 1.08, 95% confidence interval 1.00-1.16). CONCLUSION: Utilisation of cystectomy for bladder cancer in routine practice has increased over time with no evidence of a significant difference in CSS between radiotherapy and cystectomy.	bladder
A small-molecule inhibitor of PIM kinases as a potential treatment for urothelial carcinomas.	The proto-oncogene proviral integration site for moloney murine leukemia virus (PIM) kinases (PIM-1, PIM-2, and PIM-3) are serine/threonine kinases that are involved in a number of signaling pathways important to cancer cells. PIM kinases act in downstream effector functions as inhibitors of apoptosis and as positive regulators of G1-S phase progression through the cell cycle. PIM kinases are upregulated in multiple cancer indications, including lymphoma, leukemia, multiple myeloma, and prostate, gastric, and head and neck cancers. Overexpression of one or more PIM family members in patient tumors frequently correlates with poor prognosis. The aim of this investigation was to evaluate PIM expression in low- and high-grade urothelial carcinoma and to assess the role PIM function in disease progression and their potential to serve as molecular targets for therapy. One hundred thirty-seven cases of urothelial carcinoma were included in this study of surgical biopsy and resection specimens. High levels of expression of all three PIM family members were observed in both noninvasive and invasive urothelial carcinomas. The second-generation PIM inhibitor, TP-3654, displays submicromolar activity in pharmacodynamic biomarker modulation, cell proliferation studies, and colony formation assays using the UM-UC-3 bladder cancer cell line. TP-3654 displays favorable human ether-à-go-go-related gene and cytochrome P450 inhibition profiles compared with the first-generation PIM inhibitor, SGI-1776, and exhibits oral bioavailability. In vivo xenograft studies using a bladder cancer cell line show that PIM kinase inhibition can reduce tumor growth, suggesting that PIM kinase inhibitors may be active in human urothelial carcinomas.	bladder
[Down-regulation effect of TGF-beta1 on expression of VEGF in bladder cancer cell line].	OBJECTIVE: To explore the down-regulation effect of transforming growth factor-beta1 (TGF-beta1) on the expression of vascular endothelial growth factor (VEGF) in bladder cancer cell line EJ cell strain. METHODS: The siRNA expression vectors of TGF-beta1, gene were constructed, the highest inhibition target sequence was screened and selected by real time-PCR and ELISA, and then the vectors were transfected into EJ cells, the expression level of VEGF mRNA was detected by Real time-PCR. RESULTS: TGF-beta1 targeting expression vectors were successfully constructed, Real time-PCR and ELISA screened the highest inhibition target sequence (the lowest expression level of TGF-beta1 mRNA was 0.92 +/- 0.19; ELISA result was 50.08 +/- 5.85). The relative expression level of VEGF mRNA in TGF-beta1 siRNA group was the lowest, indicating that the expression of VEGF was decreased by silencing TGF-beta1, gene. CONCLUSION: Inhibition of TGF-beta1 gene expression could down regulate the expression of VEGF in bladder neoplasm.	bladder
Bladder exstrophy: current management and postoperative imaging.	Bladder exstrophy is a rare malformation characterized by an infra-umbilical abdominal wall defect, incomplete closure of the bladder with mucosa continuous with the abdominal wall, epispadias, and alterations in the pelvic bones and muscles. It is part of the exstrophy-epispadias complex, with cloacal exstrophy on the severe and epispadias on the mild ends of the spectrum. Bladder exstrophy is the most common of these entities and is more common in boys. The goal of this paper is to describe common methods of repair and to provide an imaging review of the postoperative appearances.	bladder
[Complications and their management after urinary diversion].	BACKGROUND: Bladder cancer is a common disease. It is predicted that 11,900 men and 4,500 women in Germany will be diagnosed with invasive bladder cancer in 2014. The cystectomy, which is standard treatment in muscle-invasive bladder cancer, requires urinary diversion. PURPOSE: The goal of this article is to present the complications associated with urinary diversions and their management. METHODS: Based on a selective literature search in PubMed and our own clinical experience, the options for urinary diversion and their management are discussed. RESULTS: In patients treated with curative intent, orthotopic bladder replacement is preferred. In patients with palliative intent, incontinent cutaneous urinary diversion is commonly used. The present work shows the variety of early and late complications, peri-/postoperative mortality, and the management of these patients. CONCLUSION: After cystectomy, various methods for urinary diversion are available, which can be used in curative and/or palliative intent. Crucial to the success and the long-term satisfaction of the patients is selection of the right urinary diversion method.	bladder
Urinary bladder cancer in dogs, a naturally occurring model for cancer biology and drug development.	Each year more than 65,000 people are diagnosed with urinary bladder cancer, and more than 14,000 people die from the disease in the United States. Studies in relevant animal models are essential to improve the management of bladder cancer. Naturally occurring bladder cancer in dogs very closely mimics human invasive bladder cancer, specifically high-grade invasive transitional cell carcinoma (TCC; also referred to as invasive urothelial carcinoma) in cellular and molecular features; biological behavior, including sites and frequency of metastasis; and response to therapy. Canine bladder cancer complements experimentally induced rodent tumors in regard to animal models of bladder cancer. Results of cellular and molecular studies and -omics analyses in dogs are expected to lead to improved detection of TCC and preneoplastic lesions, earlier intervention, better prediction of patient outcome, and more effective TCC management overall. Studies in dogs are being used to help define heritable risks (through very strong breed-associated risk) and environment risks and to evaluate prevention and treatment approaches that benefit humans as well as dogs. Clinical treatment trials in pet dogs with TCC are considered a win-win scenario by clinician scientists and pet owners. The individual dog benefits from effective treatment, the results are expected to help other dogs, and the findings are expected to ultimately help humans with TCC. This article provides an overview of canine TCC, a summary of the similarities and differences between canine and human invasive TCC, and examples of the types of valuable translational research that can be done using dogs with naturally occurring TCC.	bladder
ADAM10 regulates proliferation, invasion, and chemoresistance of bladder cancer cells.	A disintegrin and metalloprotease 10 (ADAM10) is upregulated in several cancers and associates with malignant cancer progression. However, its expression pattern in bladder cancer remains unexplored. In the present study, we examined ADAM10 expression in 105 bladder cancer specimens using immunohistochemistry. We found ADAM10 overexpression in 51 of 105 (48.5 %) bladder cancer specimens. ADAM10 overexpression associated with advanced tumor stage (p = 0.001) and tumor grade (p = 0.018). To explore its biological functions in bladder cancer cells, small interfering RNA (siRNA) knockdown was performed in 5,637 and T24 cell lines. Cell Counting Kit-8 (CCK8) assay and Matrigel invasion assay showed that ADAM10 depletion decreased cell proliferation, migration, and invasion. In addition, ADAM10 knockdown increased the level of cisplatin-induced apoptosis. In conclusion, ADAM10 is overexpressed in bladder cancer and regulates malignant cell growth and invasion, which makes it a candidate therapeutic target.	bladder